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Purpose: The aim of this study is to compare the interfractional setup reproducibility of two types of patient immobilization devices for prostate cancer receiving image-guided radiation therapy (IGRT). Materials and Methods: The MOLDCARE (MC) involves hydraulic fixation, whereas the BlueBAG (BB) and Vac-Lock (VL) involve vacuum fixation. For 72 patients, each immobilization device was individually customized during computed tomography (CT) simulation. Before the treatment, bony registration was performed using orthogonal kV images and digitally reconstructed radiographs. The shift of the treatment couch was recorded as a benchmark in the first session. In subsequent sessions, the shifts from the benchmark were measured and analyzed. Soft-tissue registration was performed weekly by cone-beam CT and CT images, and the shifts were measured and analyzed. Results: In the superior-inferior and left-right directions, there were nearly no changes in the overall mean among the immobilization devices. In the anterior-posterior (AP) direction, the overall mean for the MC, BB, and VL were 0.34 ± 1.33, -0.47 ± 1.27, and -1.82 ± 1.65 mm, respectively. The mean shifts along the AP direction were approximately 1 mm more in patients immobilized on the BB and 2.5 mm more in those on the VL, compared to those on the MC, after the twentieth treatment. No significant changes were observed among the patients immobilized on those devices, respectively, in soft-tissue registration. Conclusion: It can be concluded that the settling of the vacuum fixation was caused by air leakage in the latter-half treatment, and the immobilization device type has no effect on the treatment-position reproducibility in IGRT. [ABSTRACT FROM AUTHOR]